Analgesic comparison between topical irrigation (splash block) versus injection of lidocaine on the ovarian pedicle in canine ovariectomy

Abstract Objectives The aim of this study was to compare the analgesic efficacy of topical irrigation versus injection of lidocaine on the ovarian pedicle to provide analgesia in bitches ovariectomy. In the current study were monitored: increased blood pressure, heart rate and respiratory rate to identify an acute intraoperative nociceptive response. These parameters were registered at six times during the surgical procedure: grasping of the ovary (time 1), dissection of the mesosalpinx (time 2), tightening of the first loop ligature (time 3), tightening of the second loop ligature (time 4), transection of the ovarian pedicle (time 5) and release of the ovary (time 6). Material and Methods Forty healthy bitches were randomly assigned in two groups (n = 20) to receive topical irrigation (splash block) of 2% lidocaine (C group) on both ovarian pedicle (2 mg/kg each), or an equal volume of lidocaine was injected at the same sites (R group). Results The results of the present study suggest that splash block may provide intraoperative analgesic effects equivalent to injection in the ovarian pedicle in dogs that have undergone ovariectomy. The lidocaine improved surgical analgesia during canine ovariectomy in both groups, and this action is not affected by the inoculation technique. Clinical significance Pain management in veterinary patients is a crucial component of appropriate patient care. Therefore, the need for achieving safer anaesthesia for surgical intervention is gaining much attention. Ovariectomy is a common surgical procedure in bitches with medium level of pain. This study concluded that considering its relative simplicity, low cost, and safety, both techniques could be used in daily clinical practice.


INTRODUCTION
Ovariectomy is a common surgical procedure in small animal practice, useful for reducing the stray population (Dongaonkar et al., 2019), obtaining therapeutic and behavioural benefits on neutered patients , and is used as a clinical model for pain assessment studies (Wagner et al., 2008). In fact, despite the surgical simplicity of execution, ovariectomy is a surgery with medium level of pain and requires a good analgesic technique , Gaynor & Muir, 2015. Many studies have been conducted to reduce the surgical pain, such as the use of local anaesthetic, to improve intraoperative analgesia with minimal systemic side effects, decreasing surgical stress response and reducing the patient's need of a rescue analgesia (Adin, 2011;. Surgical analgesia is important because pain induces various negative effects that prevent the patient from recovering , such as a negative protein balance, reduced food intake, release of stress hormones, self-mutilation and immunosuppression , Gaynor, 1999. In several studies, local analgesics have been used in pain management in spayed domestic animals , Leoci et al., 2019. Splash block is an analgesic technique already described by several authors (Garwood et al., 2002, Tan et al., 2011, Wagner et al., 2008, Zilberstein et al., 2008 in domestic animals, which consists of an irrigation of lidocaine in the ovarian pedicle to improve local analgesia during ovariectomy. Furthermore, Grubb and Lobprise (2020) describe direct infiltration of the ovarian pedicle with lidocaine. To our knowledge, the use of lidocaine infiltrated on the canine pedicle during ovariectomy has not yet been evaluated or compared with other analgesic techniques. Although it is to be expected that additional local anaesthesia confers better analgesia, the aim of this study was to compare the analgesic efficacy of splash block versus the infiltration of lidocaine on the ovarian pedicle in bitches ovariectomy.

Study design
This was a randomized clinical research study. All bitches were enrolled over a 6-month period during 2021. The same team of surgeon performed all the procedures.

Animals
Forty bitches of various breeds presented for ovariectomy were involved in this study after obtaining informed owner consent. The female dogs were of good health, had no previous pathologies and were allocated to the very low aesthetic risk class (ASA 1). Sample size calculation was performed using G*Power for Windows Version 3.1.6 113 (Heinrich Heine Universität Düsseldorf, Germany) (Faul et al., 2007).
Exclusion criteria included aggressiveness, underlying diseases and use of analgesics or anti-inflammatory in the previous 30 days. Two days before surgery, patients underwent a comprehensive medical examination, including cardiothoracic auscultation, ECG, complete blood count (CBC), platelet count, total plasma proteins (TPP), serum creatinine, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (FA) and urea. The bitches were randomly (www.randomizer.org) assigned in two groups (n = 20) to receive topical irrigation (splash block) of 2% lidocaine (C group) on both ovarian pedicle (2 mg/kg each), or an equal volume of lidocaine was injected at the same sites (R group).

Pre-surgery
Animals were submitted to solid and water fasting of 8 and 2 hours, respectively, prior to surgery. In both groups, the bitches were premedicated with intramuscular injections of dexmedetomidine (Dexdomi-tor®, Vetoquinol Italia SRL, Bertinoro, Italy) at dosage of 3 mcg/kg and methadone (Semfortan®, Eurovet Animal Health BV, Bladel, the Netherlands) at the dosage of 0.25 mg/kg, mixed in the same syringe . The premedicants were administered into the lumbar epaxial muscles. After 20 min, a 20-G venous catheter was inserted to start a standard maintenance fluid therapy (3 ml/kg/h of ringer with lactate). Propofol (Vetofol®, Esteve, Barcelona, Spain) at 2 mg/kg was administered intravenously to induce general anaesthesia.
Orotracheal intubation was promoted, while anesthetic maintenance was performed with sevoflurane (EtSev 2,5%, SevoFlo®, Ecuphar Italia S.r.l., Milano, Italy), vaporized in 100% oxygen, in an open anesthesia system, always performed by the same anesthesiologist. During the perioperative period, the animals were continuously monitored through multiparametric monitoring heart rate, respiratory rate, noninvasive blood pressure, oxygen haemoglobin saturation and body temperature , Leoci et al., 2019.

Surgery procedure
All surgery were performed in 31 min (±5 min) from the start of the first skin incision to placement of the last skin suture. The quality of all procedures was approximately the same: the same surgeons performed all 40 procedures using a standardized surgical procedure. In C group, prior to manipulation of the ovarian pedicles, 2% lidocaine was dripped (Garwood et al., 2002, Tan et al., 2011, Wagner et al., 2008, Zilberstein et al., 2008 on the ovarian pedicle (2 mg/kg each) using a catheter urinary (splash block). In R group, 2% lidocaine was injected (Grubb & Lobprise, 2020) on the ovarian pedicle (2 mg/kg each) using a 2.5 mL syringe (23-G). Following lidocaine application, surgical manipulation was stopped for 90 s (Wagner et al., 2008, Zilberstein et al., 2008. Before the first incision (T0), the hemodynamic parameters of all animals (preincisional values of heart, respiratory and blood non-invasive pressure values) were recorded to evaluate pain responses to the surgical stimulus , Leoci et al., 2019. These parameters were registered at six time points of the study: grasping of the ovary (T1), dissection of the mesosalpinx (T2),

Data analysis
Compiled forms were entered into a database created with an Excel spreadsheet, and data analysis was performed using Stata MP17 software. Continuous variables were described as mean (standard deviation [SD]) and range, and categorical variables as proportions.

RESULTS
The population consisted of 40 bitches: 20 (50.0%) in the C group and 20 (50.0%) in the R group. The characteristics of the population according to the groups are presented in Table 1.
Repeated-measures ANOVA showed significant differences in the comparison of heart rate among different times (p < 0.0001), but not between groups (p = 0.864) or in the interaction between time and group (p = 0.317; Figure 1).
Repeated-measures ANOVA showed no significant differences in respiratory rate among various times (p = 0.151), between groups (p = 0.542) or in the interaction between time and group (p = 0.558; Figure 2).
Repeated-measures ANOVA showed a significant difference in blood pressure values among the various times (p < 0.0001), but not between groups (p = 0.0001) or in the interaction between time and group (p = 0.900; Figure 3).
The proportion of dogs undergoing rescue analgesia according to group and detection time are described in Table 2.

DISCUSSION
In this study, no significative side effects (e.g. haemorrhages, prolongation of time or cardiological alterations) were observed during the ovariectomy, and ovaries were removed without complications.
No relevant hemodynamic problems were observed as a result of surgery. All dogs recovered from anaesthesia uneventfully and within 31 min (±5 min) after switching off the isoflurane vaporizer, and no immediate postoperative complications were observed during patient awakening. The results of this study show that all animals were ovariectomized under anaesthesia with a good surgery and analgesic technique. Indeed, multimodal analgesia, including drugs administered both systemically and locally, is considered the most effective approach to providing pain relief and has been widely accepted in veterinary medicine to control intraoperative pain (Campagnol et al., 2012). The combination of general and local anaesthesia to improve the analgesic protocol has been well documented for a variety of surgical procedures (Taylor & Robertson, 2004). The results of the present study suggest that splash block may provide intraoperative analgesic effects equivalent to injection in the ovarian pedicle in dogs that have undergone ovariectomy. In fact, lidocaine is absorbed quickly from ovarian tissue and block the ascending afferent input interfering with ion channels of the nerves of ovaries, which receive sympathetic fibres from the intermesenteric and the caudal mesenteric plexus and parasympathetic fibres from the vagus nerve (Katz et al., 1992). In this study, we choose to evaluate intraoperative hemodynamic parameters: blood pressure, heart rate and respiratory rate to identify a surgical nociceptive response. In literature, the correlation between these three parameters and surgical pain is commonly used (Weary et al., 2006). In fact, when the sympathoadrenal system is stimulated by a nociceptive stimulus, hemodynamic parameters increase (Zbinden et al., 1994, Eoh et al., 2018. In this study, there was no statistical difference between the R and C groups in the blood pressure, heart rate and respiratory rate. The trends observed in physiological parameters in two groups were statistically similar (Figures 1, 2 and 3). This study showed that the integration of lidocaine in routinely anaesthetic protocols is helpful to reduce the surgical nociceptive stimulus. Indeed, lidocaine when applied topically or infiltrated acts to stop the transmission of noxious stimuli (Torske & Dyson, 2000) and offers appropriate analgesia. Lidocaine has a fast onset (< 2 min) and short duration of action (1-2 h), so it is appropriate in ovarian manipulation (Fink & Schofield, 1970).
The advantage is that this blockage desensitises the tissues innervated, providing excellent analgesia without side effects or respiratory depression (Collins et al., 2013). Carpenter et al. (2004) stated that lidocaine should be used in reproductive system surgical procedures, regardless of the administration technique (Feldman et al., 1989). In addition, considering the same low index of intraoperative rescue analgesia (Table 2) in both groups, it can be assumed that this treatment is effective enough to maintain physiological parameters at T1, T3 and T4.
In fact, the grasping of the ovary, tightening of the first loop ligature and tightening of the second loop ligature are the moments correlated with greater autonomic stimulation in ovariectomy surgery . Excessive local anaesthetic absorption can cause systemic toxicity (Feldman et al., 1989). An excessive volume of local anaesthetic could migrate cranially to the point of blockade of the nerves controlling the diaphragm, with pulmonary problems (Grubb & Lobprise, 2020, Sakura et al., 1998. The recommendation is not to exceed 20.8 ± 4 mg/kg and 6 ml for dog of lidocaine volume to prevent this complication (Grubb & Lobprise, 2020, Sakura et al., 1998. In this study, the dosage of lidocaine used was 4 mg/kg and maximum 3 ml for dog during the entire surgical procedure; therefore, it was not associated with systemic toxicity.

CONCLUSIONS
The present study showed that lidocaine administered by splash block or injection in the ovarian pedicle, during canine ovariectomy, is equivalent. This technique is not affected by the inoculation technique and confers satisfactory intraoperative analgesia during surgery procedure. Considering the cost, availability, and side effects of lidocaine, routine use of this local anaesthetic is considered desirable in bitch ovariectomy.